In a study of cognitively healthy adults, elevated levels of two biomarkers measured in the blood, GDF15 and NT-proBNP, were associated with an increased risk of developing dementia in later life.
Research from Boston University, Harvard Medical School and NUI Galway’s HRB-Clinical Research Facility, has identified two blood biomarkers that could help identify those at risk of developing dementia later in life. The study was published recently in the Journal of the American Heart Association.
Potential biomarkers
The researchers measured blood levels of (GDF15) (a biomarker of vascular stress, thought to play a role in inflammation) and (NT-proBNP) (a biomarker of an enlarged heart, associated with worsening heart failure), both potential biomarkers for dementia, in almost 1,600 participants from the Framingham Heart Study.
The research team found that GDF15 and NT-proBNP blood levels were associated with an increased risk of dementia as well as signs of vascular injury on MRI brain scans.
When combined with traditional risk factors for dementia (e.g. age, high blood pressure, or a history of heart disease), these two biomarkers improved dementia risk classification suggesting their potential use in predicting dementia risk.
Dr Emer McGrath, HRB-Clinical Research Facility Galway, NUI Galway. Photo: Aengus McMahon
Dr Emer McGrath, consultant eunrologist and lead author of the study at NUI Galway and investigator with the Framingham Heart Study (the research was completed during her previous position at Harvard Medical School), said: “Identifying biomarkers for dementia could improve our ability to predict a person’s risk of dementia and his or her future outcomes.
Current strategies limited
"Establishing which individuals are at increased risk of developing dementia, including Alzheimer’s disease, is key to developing new therapies to slow or reverse cognitive symptoms. However, current strategies are limited, both in terms of accuracy and the ability to incorporate them into routine practice.
"Unlike cerebrospinal fluid biomarkers that require a spinal tap [lumbar puncture], plasma biomarkers can be extracted from the blood, making their collection much less invasive and much more appealing for patients.
"Novel biomarkers could also help to monitor dementia severity and progression and select suitable participants for future clinical trials.”
While GDF15 has previously been associated with heart attacks, this is the first study to demonstrate an association between GDF15 and later-life dementia risk. The authors also confirmed an association between NT-proBNP levels and risk of dementia, combining their results with those from a Japanese cohort.
Dr McGrath added: "Our findings validate the results of previous studies within a community-based setting. Blood levels of NTproBNP are already routinely measured clinically in patients with heart failure.
"If we could identify appropriate clinical cut-offs for dementia, blood levels of this biomarker could prove to be useful for predicting the risk of dementia in patients.”
More diverse populations
The authors caution that the Framingham Heart Study Offspring cohort is predominantly Caucasian, which may limit the generalisability of the findings to more diverse populations.
They were also unable to explore the association between changes in plasma biomarker values over time and cognitive outcomes. Further studies will be required to replicate and validate the authors’ observed association between plasma GDF15 and dementia.
Funding for this work was provided by an Alzheimer’s Association Clinician Scientist Fellowship, the National Heart Lung and Blood Institute, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke.
The full study is available at https://www.ahajournals.org/doi/full/10.1161/JAHA.119.014659